se;condary tumors and metastasis. 



73 



internally developed secondary tumors contain the parasitic bacterium the same as the 

 primary tumors, but it is not abundant in any of the tissues. The bacterium causing the 

 disease has been found also sparingly in the strand connecting primary and secondary 

 tumors. 



Much difficulty has been experienced in stain- 

 ing Bad. iumefaciens in the tissues of the daisy, and 

 ideal preparations are yet to be obtained. It would 

 seem from an examination of numerous slides, and 

 also from the results of many poured plates, that 

 the organism occurs in the tissues of the tumor in 

 rather small numbers, especially as compared with 

 the organism causing the olive-tubercle. From what 

 I have seen I believe it occurs only inside the paren- 

 chyma cells, stimulating them to divide and passing 

 on from mother cells to daughter cells in this manner. 



The development of these tumors depends 

 on a very delicate series of adjustments between 

 the attacking organism and the host cells. My 

 present hypothesis as to the mechanism of the 

 tumor development in crown-gall is as follows: 

 Through wounds which have not injured the cells 

 beyond the power of recovery (needle-pricks in case 

 of my experiments) the bacterium gains an entrance 

 into the cell; here it multiplies rapidly for a short 

 time; its further growth is checked by the appear- 

 ance of acid to which it is very sensitive — this acid 

 being developed in the cell as a by-product of the 

 bacterial action on sugar; the first effect of the 

 acid is to inhibit the further growth of the bacteria 

 and consequently there never can be very many 

 bacteria in any individual cell; the continued 

 action of this acid on the bacteria leads to the pro- 

 duction of involution forms (clubs and Y's) and 

 finally a portion of these bacteria are killed out- 

 right, but the concentration of the acid is not suffi- 

 cient to destroy the host cell; the nucleus of the 

 latter now divides, either under the direct stimulus 

 of the acid, or under the influence of bacterial 

 endotoxins which now for the first time have been 

 liberated, i. e., have come into contact with the 

 nucleus by diffusion through the permeable mem- 

 branes of the dead bacteria; during the cell-division the bacteria are carried over into the 

 daughter cells, where under the new conditions those not destroyed by the acid multiply 

 rapidly for a short time; then in turn their growth is checked by more acid, whereupon 

 ensue the other changes ending in another cell division. In this way is developed first the 

 primary tumor, then the strands penetrating the sound tissues in various directions, and 

 finally the secondary tumors, which I have elsewhere called metastatic tumors, but which 

 are probably not so in the sense that loose tumor cells migrate from the primary tumor to 



*FiG. 24. — Leaf of Paris daisy {Chrysanthemum frutescens) developing internal tumors at points marked by letter 

 X and beyond. The lower one has split open surface of rib, others are still sub-epidermal. Source of infection was 

 the stem-tumor here shown, which was induced by needle-punctures introducing Bacterium tvmefaciens. Photo- 

 graphed Feb. 12, 1908. 



Fig. 24.* 



